摘要
目的探讨黄芩素对多发性骨髓瘤(MM)细胞增殖和迁移能力的影响及分子机制。方法以不同浓度黄芩素处理MM细胞株RPMI8226和U266细胞不同时间后,应用四甲基偶氮唑盐(MTY)比色实验检测黄芩素对MM细胞增殖的影响;用黄芩素和(或)IL-6处理RPMI8226、U266细胞,激光共聚焦及Westernblot检测处理前后细胞中β连环素(β-catenin)蛋白表达;Transwell小室实验检测不同浓度黄芩素处理前后RPMI8226和U266细胞的迁移能力;RT-PCR检测不同浓度黄芩素处理前后细胞内β-catenin、C—myc、细胞周期素D1(CyclinD1)和细胞迁移相关基因整联蛋白β7(integrin137)基因mRNA表达。结果黄芩素呈浓度和时间依赖性抑制RPMI8226和U266细胞的增殖;激光共聚焦及Westernblot结果显示黄芩素能够抑制β-catenin的表达从而抵抗IL-6对MM细胞的促增殖作用;RT—PCR检测显示黄芩素能够抑制β-catenin、c—myc、cyclinD1和integrin β7的mRNA表达;Transwell小室迁移实验表明,在基质细胞衍生因子(SDF-1)的趋化下,黄芩素以浓度依赖的方式降低MM细胞的迁移能力。结论黄芩素具有抑制MM细胞增殖和迁移的作用,其分子机制与抑制增殖相关基因β-catenin、c—myc、cyclinD1和integrinB7的表达有关。
Objective To investigate the effect of baicalein on proliferation and migration of multiple myeloma(MM) cell lines and its molecular mechanism. Methods The MM cell line RPMI-8226 and U266 cells were used as the model, and treated with different concentration and time of baicalein the effect of baica- lein on the MM ceils proliferation was assessed by MTT assay. With or without baiealein or Interleukin-6( IL- 6) treatment, the β-eatenin protein level was analyzed by immunofluoreseenee assay and western blot assay and mRNA levels of β-catenin, e-myc, cyclin D1 and integrin 7 gene by RT-PCR. Transwell chamber migra- tion assay was used to detect the cells migration ability with different concentration of baiealein cultured. Re- sults Baicalein inhibited the MM cell line RPMI 8226 and U266 cell proliferation in a dose- and time-de- pendent manner. It simultaneously inhibited β-catenin protein level to resist the effect of IL-6 on inducing MM cell proliferation, and resulted in decrease of β-catenin, c-myc, cyclinD1 and integrin β7 mRNA levels. Ba- icalein also decreased migration ability of MM cells in a dose-dependent manner by SDF-1. Conclusion Ba- icalein can inhibit MM cells proliferation and migration, and its molecular mechanisms are associated with in- hibition of proliferation related genes β-catenin, c-mye, eyclinD1 and integrin β7 expression.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2012年第11期938-943,共6页
Chinese Journal of Hematology
基金
湖北省自然科学基金(2010CDA041)